The present invention, in some embodiments thereof, relates to methods of promoting nerve growth or regeneration.
Injury to the nervous system is often associated with permanent impairment. Though peripheral nerve has a high regenerative potential, spontaneous regeneration leading to recovery of function rarely occurs after nerve transection, and the outcome of therapeutic intervention as microsurgical suturing, autologous grafting and use of nerve conduits is usually incomplete [1]. The majority of peripheral nerve injuries occur in the upper limb and are due to traumatic causes. These injuries disproportionately afflict young healthy civilians and military officers who are at risk of traumatic injuries. Severe nerve injury has a devastating impact on a patients' quality of life. Typical symptoms are sensory and motor function defects that can result in complete paralysis of the affected limb or development of intractable neuropathic pain [2]. In peacetimes these injuries account for about 5% of all admitted traumas, but during wartimes their prevalence is much higher [3]. Peripheral nerves contain myelinated motor and sensory axons, as well as unmyelinated sensory and autonomic axons. As mentioned above, the neurons partially regenerate their axons after injury, and the Schwann cells within the denervated nerve pathways support the regenerating axons and remyelinate the large ones [1]. However, exon regeneration is a slow process, progressing at speeds of 1 and 3 mm/day in humans and animals, respectively [4]. In human patients the outcome of nerve regeneration varies widely, depending on the extent and severity of injury and the distance and time required for axons to regenerate. Hence, functional outcomes after nerve injuries are frequently disappointing. Lately, several reports describing different aspects of the beneficial role mesenchymal stem cells (MSC) have during peripheral nerve regeneration were published. Guo et al. [5] described the neurotropic paracrine effects of application of human MSCs to site of injured sciatic nerve. Wakao et al. [6] demonstrated that MSCs have the potential to differentiate into Schwann cells. Biological conduits (tube implants) and vein conduits lined with MSCs were shown to have better healing potential in animal models than the same conduits without MSC [7, 8].
Recombinant human amelogenin protein (rHAM+) was previously reported to support significant and progressive regeneration of the tooth-supporting (periodontal) tissues: alveolar bone, periodontal ligament and cementum (a thin mineralized layer covering the tooth root), through recruitment of MSC [10]. Additionally, fraction C of amelogenin has been implicated in neurogenesis (WO2011077086).
Additional background art includes: Deutsch et al. 2006 Eur. J. Oral. Sci. 114:183-189; Gruenbaum et al. 2009 J. Exp. Zool. 312B:445-457; WO2011077086; US20110312891; Hanhan et al., Journal of Cell Molecular Medicine, 2016, 20(5):815-24; and WO2012/153333.